Contributions
Abstract: PB2519
Type: Publication Only
Background
Metabolic syndrome (MS) is characterized by dyslipidemia, hyperglycemia, insulin resistance. This pathology lead to the development of atherosclerotic changes in blood vessels and haemostasis disorders. The hyperactivity of platelets is the most important among the mechanisms involved in the processes of atherothrombosis. Also the development of MS lead to formation of large hyperactive platelets and increase of red blood cells hemolysis, which results an enhancement of the erythrocyte ADP release. This contributes to increased platelet aggregation, hypercoagulation and formation of prothrombogenic status of the organism. Directed influence of pharmacology agents may to reduce pathologically increased platelet aggregation. Earlier it was shown that regulatory oligopeptides exhibit anticoagulant and antiplatelet effects in the organism. Recently, special attention has been paid to proline-containing peptides with the addition of various amino acids to their molecules.
Aims
To study the increase of platelets aggregation function in rats with experimental metabolic syndrome and the possibility of its correction by short regulatory proline- and glycine-containing (glyproline) peptides Pro-Gly-Pro (PGP), Arg-Pro-Gly-Pro (RPGP), Pro-Gly-Pro-Leu (PGPL) and Pro-Gly-Pro-Val (PGPV).
Methods
The experiments were carried out on male adult (4 months of age) Wistar rats (350-400 g body weight). All experimental procedures were performed in accordance with the ethical principles of the Helsinki Declaration. Experimental MS was induced by feeding the rats a fat-rich high-caloric diet (HCD) during 6 weeks. At the same time rats received 10% glucose ad libitum. Than MS-rats were intranasally administered peptides PGP, RPGP, PGPL and PGPV at doses 200 μg/kg body weight once a day for 7 days (treated groups) and saline (control group) by simultaneous HCD continuation. ADP-induced platelet aggregation were measured in rich platelet blood plasma (Born method). Blood were collected from the jugular vena 20 h and 7 days after the last peptides administration.
Results
Experiments showed that consumption of HCD by the rats over 6 weeks lead to development of lipid and carbohydrate metabolism disorders and marked hypercoagulation. First of all, platelet aggregation increased more than twofold relative to those of normal rats. The intranasal administration of PGP, RPGP, PGPL and PGPV to MS-rats resulted a reduction of ADP-induced platelet aggregation respectively by 33%, 34%, 30% and 58% compared with control group 20 h after the last peptides injection. These effects were observed 7 days after peptides withdrawal too: ADP-induced platelet aggregation was decreased by 30%, 50%, 30% and 33% respectively. RPGP and PGPV had the most pronounced and stable antiplatelet effects in rats with experimental MS and these effects were long lasting.
Conclusion
Thus the presented study indicate that proline- and glycine-containing peptides have significant antithrombotis effects in rats with disorders of lipid and carbohydrate metabolism. They have antiplatelet effect and protect the organism from enhanced platelet aggregation, decrease activation of platelet haemostasis and thrombus formation. We assume that regulatory glyproline oligopeptides can be attributed to antithrombotic agents with anticoagulant and antiplatelet properties in metabolism disorders.
Session topic: 35. Thrombosis and vascular biology & translational Research
Keyword(s): Aggregation, Anti-platelet therapies, Peptide, Thrombosis
Abstract: PB2519
Type: Publication Only
Background
Metabolic syndrome (MS) is characterized by dyslipidemia, hyperglycemia, insulin resistance. This pathology lead to the development of atherosclerotic changes in blood vessels and haemostasis disorders. The hyperactivity of platelets is the most important among the mechanisms involved in the processes of atherothrombosis. Also the development of MS lead to formation of large hyperactive platelets and increase of red blood cells hemolysis, which results an enhancement of the erythrocyte ADP release. This contributes to increased platelet aggregation, hypercoagulation and formation of prothrombogenic status of the organism. Directed influence of pharmacology agents may to reduce pathologically increased platelet aggregation. Earlier it was shown that regulatory oligopeptides exhibit anticoagulant and antiplatelet effects in the organism. Recently, special attention has been paid to proline-containing peptides with the addition of various amino acids to their molecules.
Aims
To study the increase of platelets aggregation function in rats with experimental metabolic syndrome and the possibility of its correction by short regulatory proline- and glycine-containing (glyproline) peptides Pro-Gly-Pro (PGP), Arg-Pro-Gly-Pro (RPGP), Pro-Gly-Pro-Leu (PGPL) and Pro-Gly-Pro-Val (PGPV).
Methods
The experiments were carried out on male adult (4 months of age) Wistar rats (350-400 g body weight). All experimental procedures were performed in accordance with the ethical principles of the Helsinki Declaration. Experimental MS was induced by feeding the rats a fat-rich high-caloric diet (HCD) during 6 weeks. At the same time rats received 10% glucose ad libitum. Than MS-rats were intranasally administered peptides PGP, RPGP, PGPL and PGPV at doses 200 μg/kg body weight once a day for 7 days (treated groups) and saline (control group) by simultaneous HCD continuation. ADP-induced platelet aggregation were measured in rich platelet blood plasma (Born method). Blood were collected from the jugular vena 20 h and 7 days after the last peptides administration.
Results
Experiments showed that consumption of HCD by the rats over 6 weeks lead to development of lipid and carbohydrate metabolism disorders and marked hypercoagulation. First of all, platelet aggregation increased more than twofold relative to those of normal rats. The intranasal administration of PGP, RPGP, PGPL and PGPV to MS-rats resulted a reduction of ADP-induced platelet aggregation respectively by 33%, 34%, 30% and 58% compared with control group 20 h after the last peptides injection. These effects were observed 7 days after peptides withdrawal too: ADP-induced platelet aggregation was decreased by 30%, 50%, 30% and 33% respectively. RPGP and PGPV had the most pronounced and stable antiplatelet effects in rats with experimental MS and these effects were long lasting.
Conclusion
Thus the presented study indicate that proline- and glycine-containing peptides have significant antithrombotis effects in rats with disorders of lipid and carbohydrate metabolism. They have antiplatelet effect and protect the organism from enhanced platelet aggregation, decrease activation of platelet haemostasis and thrombus formation. We assume that regulatory glyproline oligopeptides can be attributed to antithrombotic agents with anticoagulant and antiplatelet properties in metabolism disorders.
Session topic: 35. Thrombosis and vascular biology & translational Research
Keyword(s): Aggregation, Anti-platelet therapies, Peptide, Thrombosis